Those factors that control sodium reabsorption by the kidney and maintain external sodium balance have been the focus of many investigative efforts. Analysis of sites of altered reabsorption of fluid and electrolytes by micropuncture in a variety of physiological and pathophysiological states have been hampered, however, because of the effects of anesthesia and surgery to reduce sodium excretion to only 10 or 20% of values seen in the unanesthetized animal. The ability to delineate nephron sites of altered electrolyte reabsorption becomes particularly difficult when making group comparisons since all animals, regardless of preanesthesia conditions, excrete salt at similarly low rates. Our preliminary results confirm the findings of others that this reduction in salt excretion is caused by a marked shift of vascular volume into the extravascular space. Restoration of intra- and extravascular volumes to normal by infusion of hyperoncotic isotonic plasma returns sodium and potassium excretion rates and urine osmolality to values seen in the awake animal. Using infusion of hyperoncotic plasma as a standard procedure the objectives of this proposal include: 1) A study of the nephron site(s) and mechanism(s) of altered reabsorption of salt and water in rats maintained on different salt diets, 2) a reevaluation of the mechanism(s) of escape from the salt retaining effects of the hormone deoxycorticosterone (DOCA), 3) a reinvestigation of alterations in salt and water reabsorption in chronically volume depleted rats, and 4) an examination of glomerular dynamics and salt and water reabsorption in the early stages of experimental hypertension together with an examination of the site of action of various antihypertensive agents. The design of these studies will allow us to examine sites of alterations of salt and water reabsorption at the single nephron level for the first time in animals which are excreting salt and water and concentrating their urine in amounts appropriate for the dietary intake and urinary output of the awake animal. The protocol will also permit examination of the dynamics of glomerular ultrafiltration in DOCA hypertension and will allow us to study the mechanism of action of anti-hypertensive agents on the pre-and postglomerular vasculature.